Purpose :
C1q and tumor necrosis factor-related protein (CTRP) 6 has recently been confirmed as an inhibitor of the alternative pathway of complement activation (APC), sharing the same target (C3bBb) in APC with complement factor H (CFH). However, there has yet to be an investigation on the linkage of CTRP6 with age-related macular degeneration (AMD) pathogenesis, including the localization of CTRP6 in the human retina. This study investigated the localization of CTRP6 in the retina of human AMD eyes and the distinct localization patterns of CTRP6, other complement activation regulatory factors, and complement components.

Methods :
Caucasian donor eyes diagnosed as AMD during the donor’s lifetime (obtained from SightLife Inc., Seattle, WA, USA) were used for this study. Donor eyes without retinal abnormality were used as non-AMD controls. The eyes were cut into a posterior eye-cup, embedded, and frozen. Sections were then made and stained with hematoxylin-eosin to evaluate histological changes in the retina. Immunohistochemical staining using anti-CTRP6, -CTRP5, -CTRP10, -CFH, -CD59, -Clusterin (CLU), -C3, and -CFB antibodies was also performed. The stained sections were then observed to assess the localization of CTRP6 and other molecules in the outer retina and choroid.

Results :
High expression of CTRP6 and CLU was evident in the drusen of the AMD eyes. However, no expression of CTRP6 was observed in the normal retinal pigment epithelium (RPE) of the AMD and non-AMD eyes. Expression of CTRP6 and CLU was also observed in the Bruch’s membrane and choroid. Expression of CD59 was observed not only in the drusen of the AMD eyes, but also in the normal RPE, Bruch’s membrane, and choroid of the AMD and non-AMD eyes. C3 and CFB which associate with APC were focally observed in the drusen of the AMD eyes. No characteristic localization pattern was observed for CTRP5 and CTRP10.

Conclusions :
Expression of CTRP6, CLU, C3, and CFB which associate with APC was observed in the drusen of AMD eyes, supporting the association of CTRP6 and CLU (selective inhibitors of APC) with the pathogenesis of AMD. Further detailed study is needed to discriminate the role of CTRP6 from CFH in the pathogenesis of AMD.

This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.